Use of Cancer-Directed therapy at the end of life among adolescents and young adults.

BACKGROUND: Adolescents and young adults (AYAs) frequently receive chemotherapy near death. We know less about use of targeted agents and immunotherapy or trends over time. METHODS: We conducted a retrospective cohort study of 1,836 AYAs with cancer who died between 2009-2019 after receiving care at one of three sites (Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California). We reviewed electronic health data and medical records to examine use of cancer-directed therapy in the last 90 days of life, including chemotherapy, targeted therapy, immunotherapy, and investigational drugs. RESULTS: Over the study period, 35% of AYAs received chemotherapy in the last 90 days of life; 24% received targeted therapy, 7% immunotherapy, and 5% investigational drugs. Fifty-six percent received at least one form of systemic cancer-directed therapy in the last 90 days of life. After adjustment for patient sex, race, ethnicity, age, site of care, diagnosis, and years from diagnosis to death, the proportion of AYAs receiving targeted therapy (odds ratio (OR) 1.05 per year of death, 95% confidence interval (CI) 1.02-1.10, P = .006), immunotherapy (OR 1.27, 95%CI 1.18-1.38, P<.0001), and any cancer-directed therapy (OR1.04, 95%CI 1.01-1.08, P=.01) in the last 90 days of life increased over time. CONCLUSIONS: More than half of AYAs receive cancer therapy in the last 90 days of life, and use of novel agents such as targeted therapy and immunotherapy are increasing over time. While some AYAs may wish to continue cancer therapy while living with advanced disease, efforts are needed to ensure that use of cancer-directed therapy meets preferences of AYAs approaching death.

Quality of End-of-Life Care Among Adolescents and Young Adults With Cancer.

Adolescents, young adults with cancer receive limited psychosocial and spiritual support near death.

Invasive Management of Hypertrophic Cardiomyopathy With Clinically Important Obstruction: Catheter Intervention Is Superior.

Hypertrophic cardiomyopathy is a common inherited cardiac condition where the myocardium progressively thickens in the absence of abnormal loading conditions. Left ventricular hypertrophy often leads to outflow tract obstruction, and this confers significant mortality and morbidity implications. Septal reduction therapies aim to relieve the obstruction in an attempt to reduce the burden of symptoms and potentially improve prognosis. However, both surgical and catheter-based approaches to septal reduction carry risks. At present, international guidelines and expert consensus statements suggest surgical myomectomy is the gold-standard treatment. In this point-counterpoint review, we discuss why in our opinion this recommendation should be reconsidered. We hope to cover the history of catheter based septal reduction therapies and the significant advances made over the last two decades. We also hope to show why we believe the current evidence shows catheter-based alcohol septal ablation is superior to surgical myomectomy.

Interventions in Hypertrophic Obstructive Cardiomyopathy.

Obstructive hypertrophic cardiomyopathy is the most common genetically transmitted cardiomyopathy that is associated with significant morbidity and mortality. Despite contemporary treatments and interventions, the management of patients with obstructive hypertrophic cardiomyopathy remains poorly defined compared with other branches of cardiology. In this review, we discuss established and novel therapeutic interventions in patients with obstructive hypertrophic cardiomyopathy with a focus on percutaneous and surgical strategies including surgical myectomy, mitral valve repair or replacement, percutaneous alcohol septal ablation, pacemaker and cardioverter-defibrillator implantation, septal embolization, radiofrequency endocardial catheter ablation, and percutaneous intramyocardial septal radiofrequency ablation.

Influence of Comorbidity Burden, Socioeconomic Status, and Race and Ethnicity on Survival Disparities in Patients With Cancer.

PURPOSE: The purpose of this study was to assess the association of comorbidity burden with overall survival, accounting for racial/ethnic and socioeconomic differences in patients with cancer. METHODS: In this retrospective cohort study, patients newly diagnosed with cancer between 2010 and 2018 were identified from a large health plan in southern California. Cancer registry data were linked with electronic health records (EHR). Comorbidity burden was defined by the Elixhauser comorbidity index (ECI). Patients were followed through December 2019 to assess all-cause mortality. Association of comorbidity burden with all-cause mortality was evaluated using Cox proportional hazards model. Crude and adjusted hazard ratio (HR, 95%CI) were determined. RESULTS: Of 153,270 patients included in the analysis, 29% died during the ensuing 10-year follow-up. Nearly 49% were patients of color, and 32% had an ECI > 4. After adjusting for age, sex, race/ethnicity, cancer stage, smoking status, insurance payor, medical center, year of cancer diagnosis, and cancer treatments, we observed a trend demonstrating higher mortality risk by decreasing socioeconomic status (SES) (P-trend<.05). Compared to patients in the highest SES quintile, patients in the lowest, second lowest, middle, and second highest quintiles had 25%, 21%, 18%, and 11% higher risk of mortality, respectively [(HR, 95%CI): 1.25 (1.21-1.29), 1.21 (1.18-1.25), 1.18 (1.15-1.22), and 1.11 (1.07-1.14), respectively]. When we additionally adjusted for ECI, the adjusted HRs for SES were slightly attenuated; however, the trend persisted. Patients with higher comorbidity burden had higher mortality risk compared to patients with ECI score = 0 in the adjusted model [(HR, 95%CI): 1.22 (1.17-1.28), 1.48 (1.42-1.55), 1.80 (1.72-1.89), 2.24 (2.14-2.34), and 3.39 (3.25-3.53) for ECI = 1, 2, 3, 4, and >5, respectively]. CONCLUSIONS: Comorbidity burden affects overall survival in cancer patients irrespective of racial/ethnic and SES differences. Reducing comorbidity burden can reduce some, but not all, of the mortality risk associated with lower SES.

Discussions About Goals of Care and Advance Care Planning Among Adolescents and Young Adults With Cancer Approaching the End of Life.

PURPOSE: Adolescents and young adults (AYAs) with cancer receive high rates of medically intensive measures at the end of life. This study aimed to characterize the prevalence and timing of conversations about goals of care and advance care planning among AYAs at the end of life as one potential influence on care received. METHODS: This was a review of electronic health data and medical records for 1,929 AYAs age 12-39 years who died after receiving care at one of three sites between 2003 and 2019, including documented conversations about goals of care and advance care planning, and care received. RESULTS: A majority of AYAs were female (54%) and White (61%); 12% were Asian, 8% Black, and 27% Hispanic. Most patients had documented discussions about prognosis (86%), goals of care (83%), palliative care (79%), hospice (79%), and preferred location of death (64%). When last documented goals of care were evaluated, 69% of patients wanted care focused on palliation; however, 29% of those with palliative goals spent time in the intensive care unit (ICU) in the last month of life, and 32% had multiple emergency room (ER) visits. When goals-of-care discussions happened earlier, >30 days before death, AYAs were less likely to receive chemotherapy in the last 14 days of life (P = .001), ICU care (P < .001), ER visits (P < .001), and hospitalizations in the last month (P < .001). CONCLUSION: High rates of medically intensive measures among AYAs near the end of life do not appear to be the result of a lack of discussions about goals of care and advance care planning. Although some interventions may be used to support palliative goals, earlier discussions have potential to reduce late-life intensive measures.

British Society of Echocardiography guideline for the transthoracic echocardiographic assessment of cardiac amyloidosis.

These guidelines form an update of the BSE guideline protocol for the assessment of restrictive cardiomyopathy (Knight et al. in Echo Res Prac, 2013). Since the original recommendations were conceived in 2013, there has been an exponential rise in the diagnosis of cardiac amyloidosis fuelled by increased clinician awareness, improvements in cardiovascular imaging as well as the availability of new and effective disease modifying therapies. The initial diagnosis of cardiac amyloidosis can be challenging and is often not clear-cut on the basis of echocardiography, which for most patients presenting with heart failure symptoms remains the first-line imaging test. The role of a specialist echocardiographer will be to raise the suspicion of cardiac amyloidosis when appropriate, but the formal diagnosis of amyloid sub-type invariably requires further downstream testing. This document seeks to provide a focused review of the literature on echocardiography in cardiac amyloidosis highlighting its important role in the diagnosis, prognosis and screening of at risk individuals, before concluding with a suggested minimum data set, for use as an aide memoire when reporting.

Engineered bacteria detect tumor DNA.

Synthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent Acinetobacter baylyi to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids, and tumors. We characterized the functionality of the biosensors in vitro with coculture assays and then validated them in vivo with sensor bacteria delivered to mice harboring colorectal tumors. We observed horizontal gene transfer from the tumor to the sensor bacteria in our mouse model of CRC. This cellular assay for targeted, CRISPR-discriminated horizontal gene transfer (CATCH) enables the biodetection of specific cell-free DNA.

Concentric and Eccentric Remodelling of the Left Ventricle and Its Association to Function in the Male Athletes Heart: An Exploratory Study.

AIMS: To compare (1) conventional left ventricular (LV) functional parameters, (2) LV peak strain and strain rate and (3) LV temporal strain and strain rate curves in age, ethnicity and sport-matched athletes with concentric, eccentric and normal LV geometry. METHODS: Forty-five male athletes were categorised according to LV geometry including concentric remodelling/hypertrophy (CON), eccentric hypertrophy (ECC) or normal (NORM). Athletes were evaluated using conventional echocardiography and myocardial speck tracking, allowing the assessment of myocardial strain and strain rate; as well as twist mechanics. RESULTS: Concentric remodelling was associated with an increased ejection fraction (EF) compared to normal geometry athletes (64% (48-78%) and 56% (50-65%), respectively; p < 0.04). No differences in peak myocardial strain or strain rate were present between LV geometry groups including global longitudinal strain (GLS; CON -16.9% (-14.9-20.6%); ECC -17.9% (-13.0-22.1%); NORM -16.9% (-12.8-19.4%)), global circumferential strain (GCS; CON -18.1% (-13.5-24.5%); ECC -18.7% (-15.6-22.4%); NORM -18.0% (-13.5-19.7%)), global radial strain (GRS; CON 42.2% (30.3-70.5%); ECC 50.0% (39.2-60.0%); NORM 40.6 (29.9-57.0%)) and twist (CON 14.9° (3.7-25.3°); ECC 12.5° (6.3-20.8°); NORM 13.2° (8.8-24.2°)). Concentric and eccentric remodelling was associated with alterations in temporal myocardial strain and strain rate as compared to normal geometry athletes. CONCLUSION: Physiological concentric and eccentric remodelling in the athletes heart is generally associated with normal LV function; with concentric remodelling associated with an increased EF. Physiological concentric and eccentric remodelling in the athletes heart has no effect on peak myocardial strain but superior deformation and untwisting is unmasked when assessing the temporal distribution.

Investigating Mortality Disparities Among Insured Patients With Colon Cancer Treated in an Integrated Health care System and Other Private Settings.

BACKGROUND: Lower socioeconomic status (SES) affects health care delivery and is associated with worse outcomes. Integrated healthcare systems (IHS) may help reduce barriers to health care and affect outcomes. Our aim was to compare outcomes of colon cancer cases diagnosed at the largest IHS in California, Kaiser Permanente Southern California (KPSC), to other insured patients (OI) to determine how SES influences mortality. METHODS: This retrospective cohort study included insured adults in southern California diagnosed with colon cancer between 2009 and 2014, using data from the California Cancer Registry, and followed through 2017. Main outcome was all-cause mortality. Person-year mortality rates were calculated for two groups, KPSC and OI. Multivariable hazard ratios were calculated for association between SES quintiles and mortality. RESULTS: Total of 15 923 patients were diagnosed with colon cancer, 4195 patients (26.3%) within KPSC and 11 728 patients (73.7%) in OI. The overall mortality rate per 1000 person-years (PY) was lower in KPSC [103.8/1000 PY (95% CI:98.5-109.3)] compared to OI [139.3/1000 PY (95% CI:135.2-143.4)]. Compared to the highest SES group, the lowest SES group did not experience higher mortality risk in the KPSC population, after adjusting for race/ethnicity and other factors (HR, 95% CI = 1.13, .93-1.38). However, in OI patients, lowest and lower-middle SES groups had higher mortality risk compared to the highest SES group (HR, 95% CI = 1.26, 1.13-1.40 and 1.28, 1.16-1.41, respectively). DISCUSSION: Lower SES was associated with higher mortality risk within the OI group; however, within KPSC no such association was observed. Care coordination in IHS settings mitigate SES-related mortality differences.

Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterised by left ventricular hypertrophy (LVH), myocardial fibrosis, enhanced oxidative stress and energy depletion. Unbound/loosely bound tissue copper II ions are powerful catalysts of oxidative stress and inhibitors of antioxidants. Trientine is a highly selective copper II chelator. In preclinical and clinical studies in diabetes, trientine is associated with reduced LVH and fibrosis, and improved mitochondrial function and energy metabolism. Trientine was associated with improvements in cardiac structure and function in an open-label study in patients with HCM. METHODS: The Efficacy and Mechanism of Trientine in Patients with Hypertrophic Cardiomyopathy (TEMPEST) trial is a multicentre, double-blind, parallel group, 1:1 randomised, placebo-controlled phase II trial designed to evaluate the efficacy and mechanism of action of trientine in patients with HCM. Patients with a diagnosis of HCM according to the European Society of Cardiology Guidelines and in New York Heart Association classes I-III are randomised to trientine or matching placebo for 52 weeks. Primary outcome is change in left ventricular (LV) mass indexed to body surface area, measured using cardiovascular magnetic resonance. Secondary efficacy objectives will determine whether trientine improves exercise capacity, reduces arrhythmia burden, reduces cardiomyocyte injury, improves LV and atrial function, and reduces LV outflow tract gradient. Mechanistic objectives will determine whether the effects are mediated by cellular or extracellular mass regression and improved myocardial energetics. CONCLUSION: TEMPEST will determine the efficacy and mechanism of action of trientine in patients with HCM. TRIAL REGISTRATION NUMBERS: NCT04706429 and ISRCTN57145331.

Development and validation of the COVID-19 Hospitalized Patient Deterioration Index.

OBJECTIVES: To develop a COVID-19-specific deterioration index for hospitalized patients: the COVID Hospitalized Patient Deterioration Index (COVID-HDI). This index builds on the proprietary Epic Deterioration Index, which was not developed for predicting respiratory deterioration events among patients with COVID-19. STUDY DESIGN: A retrospective observational cohort was used to develop and validate the COVID-HDI model to predict respiratory deterioration or death among hospitalized patients with COVID-19. Deterioration events were defined as death or requiring high-flow oxygen, bilevel positive airway pressure, mechanical ventilation, or intensive-level care within 72 hours of run time. The sample included hospitalized patients with COVID-19 diagnoses or positive tests at Kaiser Permanente Southern California between May 3, 2020, and October 17, 2020. METHODS: Machine learning models and 118 candidate predictors were used to generate benchmark performance. Logit regression with least absolute shrinkage and selection operator and physician input were used to finalize the model. Split-sample cross-validation was used to train and test the model. RESULTS: The area under the receiver operating curve was 0.83. COVID-HDI identifies patients at low risk (negative predictive value [NPV] > 98.5%) and borderline low risk (NPV > 95%) of an event. Of all patients, 74% were identified as being at low or borderline low risk at some point during their hospitalization and could be considered for discharge with or without home monitoring. A high-risk group with a positive predictive value of 51% included 12% of patients. Model performance remained high in a recent cohort of patients. CONCLUSIONS: COVID-HDI is a parsimonious, well-calibrated, and accurate model that may support clinical decision-making around discharge and escalation of care.

Patient, Family, and Clinician Perspectives on Location of Death for Adolescents and Young Adults With Cancer.

PURPOSE: Adolescents and young adults (AYAs) with cancer have high rates of hospital deaths. It is not clear if this reflects their preferences or barriers to dying at home. METHODS: Between December 2018 and January 2021, we conducted in-depth interviews with AYAs (age 12-39 years) with stage IV or recurrent cancer, family caregivers including bereaved caregivers, and clinicians of AYAs with cancer. Patients were asked about their priorities for care including location of death, caregivers were asked what was most important in the care of their AYA family member, and clinicians were asked to reflect on priorities identified through caring for AYAs. Directed content analysis was applied to interview data, and themes regarding location of death were developed. RESULTS: Eighty individuals (23 AYAs, 28 caregivers, and 29 clinicians) participated in interviews. Most AYAs and caregivers preferred a home death. However, some AYAs and caregivers opted for a hospital death to alleviate caregiver burden or protect siblings from the perceived trauma of witnessing a home death. Lack of adequate services to manage intractable symptoms at home and insufficient caregiver support led some AYAs/caregivers to opt for hospital death despite a preference for home death. Participants acknowledged the value of hospice while also pointing out its limitations in attaining a home death. CONCLUSION: Although most AYAs prefer to die at home, this preference is not always achieved. Robust home-based services for effective symptom management and caregiver support are needed to close the gap between preferred and actual location of death for AYAs.

Cardiac sarcoidosis in an adult person with cystic fibrosis: a case report.

Cardiac sarcoidosis and cystic fibrosis (CF) are both rare conditions and their co-existence has not previously been noted in adults. For the first time we report a case of isolated cardiac sarcoidosis in a woman with CF, and discuss the possible combined aetiological factors. As the life expectancy of people with CF continues to increase, clinicians should be aware of the emergence of concomitant inflammatory conditions typically diagnosed in adulthood, and the diagnostic challenges this may present.

Pediatric Acute Lymphoblastic Leukemia With Hypereosinophilia and IDH2 Gene Mutation: A Case Report and Literature Review.

Eosinophilia is a rare presentation of acute lymphoblastic leukemia (ALL) within the pediatric population. In this report, we present a patient with pre-B ALL and eosinophilia in the setting of an isocitrate dehydrogenase-2 gene mutation. These mutations have been described in patients with acute myeloid leukemia but in very few patients with ALL.

Rapid, Affordable, and Uncomplicated Production of Bacterial Cell-free Lysate.

Cell-free gene expression offers the power of biology without the complications of a living organism. Although many such gene expression systems exist, most are quite expensive to buy and/or require special equipment and finely honed expertise to produce effectively. This protocol describes a method to produce bacterial cell-free lysate that supports high levels of gene expression, using only standard laboratory equipment and requiring minimal processing. The method uses an Escherichia coli strain producing an endolysin that does not affect growth, but which efficiently lyses a harvested cell pellet following a simple freeze-thaw cycle. The only further processing required is a brief incubation followed by centrifugation to clear the autolysate of cellular debris. Dynamic gene circuits can be achieved through heterologous expression of the ClpX protease in the cells before harvesting. An E. coli strain lacking the lacZ gene can be used for high-sensitivity, cell-free biosensing applications using a colorimetric or fluorescent readout. The entire protocol requires as few as 8-9 hours, with only 1-2 hours of hands-on labor from inoculation to completion. By reducing the cost and time to obtain cell-free lysate, this method should increase the affordability of cell-free gene expression for various applications.

Patient, Family, and Clinician Perspectives on End-of-Life Care Quality Domains and Candidate Indicators for Adolescents and Young Adults With Cancer.

Importance: End-of-life care quality indicators specific to adolescents and young adults (AYAs) aged 12 to 39 years with cancer have not been developed. Objective: To identify priority domains for end-of-life care from the perspectives of AYAs, family caregivers, and clinicians, and to propose candidate quality indicators reflecting priorities. Design, Setting, and Participants: This qualitative study was conducted from December 6, 2018, to January 5, 2021, with no additional follow-up. In-depth interviews were conducted with patients, family caregivers, and clinicians and included a content analysis of resulting transcripts. A multidisciplinary advisory group translated priorities into proposed quality indicators. Interviews were conducted at the Dana-Farber Cancer Institute, Kaiser Permanente Northern California, Kaiser Permanente Southern California, and an AYA cancer support community (lacunaloft.org). Participants included 23 AYAs, 28 caregivers, and 29 clinicians. Exposure: Stage IV or recurrent cancer. Main Outcomes and Measures: Care priorities. Results: Interviews were conducted with 23 patients (mean [SD] age, 29.3 [7.3] years; 12 men [52%]; 18 White participants [78%]), 28 family caregivers (23 women [82%]; 14 White participants [50%]), and 29 clinicians (20 women [69%]; 13 White participants [45%]). Caregivers included 22 parents (79%), 5 spouses or partners (18%), and 1 other family member (4%); the 29 clinicians included 15 physicians (52%), 6 nurses or nurse practitioners (21%), and 8 social workers or psychologists (28%). Interviews identified 7 end-of-life priority domains: attention to physical symptoms, attention to quality of life, psychosocial and spiritual care, communication and decision-making, relationships with clinicians, care and treatment, and independence. Themes were consistent across the AYA age range and participant type. Although some domains were represented in quality indicators developed for adults, unique domains were identified, as well as AYA-specific manifestations of existing domains. For example, quality of life included global quality of life; attainment of life goals, legacy, and meaning; support of personal relationships; and normalcy. Within communication and decision-making, domains included communication early in the disease course, addressing prognosis and what to expect at the end of life, and opportunity for AYAs to hold desired roles in decision-making. Care and treatment domains relevant to cancer therapy, use of life-prolonging measures, and location of death emphasized the need for preference sensitivity rather than a standard path. This finding differs from existing adult indicators that propose that late-life chemotherapy, intensive measures, and hospital death should be rare. Conclusions and Relevance: The findings of this qualitative study suggest that AYAs with cancer have priorities for care at the end of life that are not fully encompassed in existing indicators for adults. Use of new indicators for this young population may better reflect patient- and family-centered experiences of quality care.

Influence of health care systems on mortality in adult patients with cancer.

OBJECTIVES: We compared all-cause mortality in insured patients with cancer who were diagnosed in Kaiser Permanente Southern California (KPSC), the largest integrated health care delivery system in southern California, with that in patients diagnosed in hospitals that serve other private insurance (OPI) plans. STUDY DESIGN: Retrospective cohort study. METHODS: Using the California Cancer Registry, we conducted a cohort analysis of all insured adults diagnosed between 2009 and 2014 with 8 common cancers (breast, prostate, lung, colon, melanoma, endometrium, kidney, and bladder) and followed them through December 2017. The cohort comprised 164,197 patients with cancer. We calculated person-year mortality rates by health care system (KPSC and OPI), and we estimated adjusted HRs for the association between overall mortality and health care system using Cox proportional hazards models accounting for race/ethnicity, demographics, cancer site, tumor characteristics, payer, cancer treatments, and socioeconomic status. RESULTS: We observed 41,727 deaths during the 9 years of follow-up. We found that the patients diagnosed in KPSC had lower overall mortality rates than in the OPI group, a difference that also held within each age category, racial/ethnic group, and stage at diagnosis. In multivariable models adjusting for relevant covariates, African American/Black patients (adjusted HR, 1.14; 95% CI, 1.06-1.21) and Hispanic patients (adjusted HR, 1.23; 95% CI, 1.16-1.30) in the OPI group had dramatically higher mortality risks than those diagnosed in KPSC. CONCLUSIONS: Among insured patients with cancer in southern California, those diagnosed within KPSC had lower overall mortality compared with the OPI group. Furthermore, this protective effect was greatest for African American/Black patients and Hispanic patients.

Patterns of overall mortality by race/ethnicity and socioeconomic status in insured cancer patients in Southern California.

PURPOSE: We evaluated the influence of race/ethnicity and geocoded socioeconomic status (SES) on all-cause mortality in cancer patients with health insurance. METHODS: We identified adults diagnosed with eight common cancers from 2009 to 2014 from the California Cancer Registry and followed them through 2017 (8 years maximum). We calculated person-year mortality rates by race/ethnicity and SES. Adjusted hazard ratios for the association between overall mortality and race/ethnicity and SES were estimated using Cox proportional hazards models accounting for other demographics, stage at diagnosis, and cancer treatments. RESULTS: A total of 164,197 adults were diagnosed with cancer originating from breast, prostate, lung, colon, skin melanoma, uterus, kidney, and bladder. For all race/ethnic groups combined, the mortality rates from lowest to highest SES groups were 112.1/1000 PY (lowest); 100.2/1000 PY (lower-middle); 91.2/1000 PY (middle); 79.1/1000 PY (upper-middle); and 63.5/1000 PY (upper). These rates suggest that person with lowest SES have a markedly increased mortality risk after cancer diagnosis even if they have health insurance. In multivariable analyses, those in the lowest SES group had a 40-78% increased risk of all-cause mortality compared to those in the upper SES group across all race/ethnicities. For example, within African Americans, the adjusted mortality risk was up to 61% higher (HR 1.61, 95% CI 1.41-1.83) in the lowest SES group compared to the highest SES group. CONCLUSION: This study suggests disparities in overall mortality risk after cancer diagnoses persist even in a cohort with health insurance, and that SES is an important driver of this disparity.

One-Day Construction of Multiplex Arrays to Harness Natural CRISPR-Cas Systems.

CRISPR-Cas systems are prokaryotic immune systems that have proliferated widely not only in bacteria and archaea, but also much more recently, in human biological research and applications. Much work to date has utilized synthetic sgRNAs along with the CRISPR nuclease Cas9, but the discovery of array-processing nucleases now allows the use of more compact, natural CRISPR arrays in heterologous hosts, in addition to organisms with endogenous systems. Unfortunately, the construction of multiplex natural CRISPR arrays remains technically challenging, expensive, and/or time-consuming. This limitation hampers research involving natural CRISPR arrays in both native and heterologous hosts. To address this problem, we present a method to assemble CRISPR arrays that is simple, rapid, affordable, and highly scalable-we assembled 9-spacer arrays with 1 day's worth of work. We used this method to harness the endogenous CRISPR-Cas system of the highly competent bacterium Acinetobacter baylyi, showing that while single spacers are not always completely effective at blocking DNA acquisition through natural competence, multiplex natural CRISPR arrays enable both nearly complete DNA exclusion and genome editing, including with multiple targets for both. In addition to demonstrating a CRISPR array assembly method that will benefit a variety of applications, we also find a potential bet-hedging strategy for balancing CRISPR defense versus DNA acquisition in naturally competent A. baylyi.